Variant 4-5745351-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153717.3(EVC):c.939+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,613,168 control chromosomes in the GnomAD database, including 362,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33943 hom., cov: 30)

Exomes 𝑓: 0.67 ( 328661 hom. )

Consequence

EVC
NM_153717.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.191

Variant links:

Genes affected

EVC (HGNC:3497): (EvC ciliary complex subunit 1) This gene encodes a protein containing a leucine zipper and a transmembrane domain. This gene has been implicated in both Ellis-van Creveld syndrome (EvC) and Weyers acrodental dysostosis. [provided by RefSeq, Jul 2008]

EVC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 4-5745351-A-G is Benign according to our data. Variant chr4-5745351-A-G is described in ClinVar as [Benign]. Clinvar id is 262784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5745351-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVC	NM_153717.3 linkuse as main transcript	c.939+10A>G		intron_variant		ENST00000264956.11	NP_714928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11 linkuse as main transcript	c.939+10A>G		intron_variant		1	NM_153717.3	ENSP00000264956	P1
EVC	ENST00000509451.1 linkuse as main transcript	c.939+10A>G		intron_variant		1		ENSP00000426774

Frequencies

GnomAD3 genomes

AF:

0.663

AC:

100741

AN:

151844

Hom.:

33920

Cov.:

show subpopulations

Gnomad AFR

AF:

0.713

Gnomad AMI

AF:

0.605

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.704

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.680

Gnomad MID

AF:

0.657

Gnomad NFE

AF:

0.680

Gnomad OTH

AF:

0.656

GnomAD3 exomes

AF:

0.621

AC:

156079

AN:

251244

Hom.:

49870

AF XY:

0.624

AC XY:

84739

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.712

Gnomad AMR exome

AF:

0.479

Gnomad ASJ exome

AF:

0.699

Gnomad EAS exome

AF:

0.351

Gnomad SAS exome

AF:

0.592

Gnomad FIN exome

AF:

0.677

Gnomad NFE exome

AF:

0.684

Gnomad OTH exome

AF:

0.646

GnomAD4 exome

AF:

0.667

AC:

973956

AN:

1461206

Hom.:

328661

Cov.:

AF XY:

0.664

AC XY:

482989

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.713

Gnomad4 AMR exome

AF:

0.491

Gnomad4 ASJ exome

AF:

0.704

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.594

Gnomad4 FIN exome

AF:

0.673

Gnomad4 NFE exome

AF:

0.689

Gnomad4 OTH exome

AF:

0.663

GnomAD4 genome

AF:

0.664

AC:

100830

AN:

151962

Hom.:

33943

Cov.:

AF XY:

0.657

AC XY:

48843

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.713

Gnomad4 AMR

AF:

0.568

Gnomad4 ASJ

AF:

0.704

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.590

Gnomad4 FIN

AF:

0.680

Gnomad4 NFE

AF:

0.680

Gnomad4 OTH

AF:

0.656

Alfa

AF:

0.688

Hom.:

10447

Bravo

AF:

0.656

Asia WGS

AF:

0.490

AC:

1708

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ellis-van Creveld syndrome

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 02, 2018	- -

Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Curry-Hall syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

3.1

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over